Publications by authors named "Robert Stewart"

755 Publications

Loneliness in older adult mental health services during the COVID-19 pandemic and before: Associations with disability, functioning and pharmacotherapy.

Int J Geriatr Psychiatry 2021 Oct 6. Epub 2021 Oct 6.

South London and Maudsley NHS Foundation Trust, London, UK.

Objectives: Loneliness is associated with psychiatric morbidity. Restrictions placed on the population during the first COVID-19 lockdown may have disproportionately affected older adults, possibly through increasing loneliness. We sought to investigate this by examining loneliness in referrals to mental health of older adults (MHOA) services during the first UK COVID-19 lockdown.

Methods: Referrals to MHOA services from a large South London catchment area were identified for the 16-week period of the UK lockdown starting in March 2020 and for the corresponding period in 2019. A natural language processing algorithm identified loneliness in the patients' records. We applied logistic regression models adjusted for age, gender, ethnicity and diagnosis, to examine associations of loneliness in the study population.

Results: 1991 referrals were identified, 56.9% of whom were female, with a mean age of 77.9 years. Only 26.9% occurred during the 2020 lockdown, but with a higher prevalence of loneliness (22.0 vs. 17.7%, p = 0.028). In the whole sample, loneliness was associated with non-accidental self-injury (Odds ratio [OR]: 1.65), depressed mood (OR: 1.73), psychotic symptoms (OR: 1.65), relationship problems (OR: 1.49), problems with daytime activities (OR: 1.36), and antidepressant use (OR: 2.11). During lockdown, loneliness was associated with non-accidental self-injury (OR: 2.52), problem drinking or drug-taking (OR 2.33), and antidepressant use (OR 2.10).

Conclusions: Loneliness is associated with more severe symptoms of affective illness, worse functional problems and increased use of antidepressant medication in older adults. During lockdown, loneliness in referrals to MHOA services increased and was associated with increased risk-taking behaviour. Loneliness is a potential modifiable risk factor for mental illness, and efforts to minimise it in older adults should be prioritised as we emerge from the pandemic.
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http://dx.doi.org/10.1002/gps.5630DOI Listing
October 2021

EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues.

J Gen Physiol 2021 11 28;153(11). Epub 2021 Sep 28.

Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA.

A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. Here, we describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. We synthesized GxTX-594, a variant of the peptidyl tarantula toxin guangxitoxin-1E, conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. We term this tool EVAP (Endogenous Voltage-sensor Activity Probe). GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane-endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. To interpret dynamic changes in fluorescence intensity, we developed a statistical thermodynamic model that relates the conformational changes of Kv2 voltage sensors to degree of labeling. We used two-photon excitation imaging of rat brain slices to image Kv2 proteins in neurons. We found puncta of GxTX-594 on hippocampal CA1 neurons that responded to voltage stimulation and retain a voltage response roughly similar to heterologously expressed Kv2.1 protein. Our findings show that EVAP imaging methods enable the identification of conformational changes of endogenous Kv2 voltage sensors in tissue.
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http://dx.doi.org/10.1085/jgp.202012858DOI Listing
November 2021

Synergistic effects of resilience and serum ghrelin levels on the 12-week pharmacotherapeutic response in patients with depressive disorders.

J Affect Disord 2021 Sep 16. Epub 2021 Sep 16.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea. Electronic address:

Background: This study investigated the individual and combined effects of self-reported resilience and serum ghrelin levels on 12-week remission in outpatients with depressive disorders who received antidepressant treatment.

Methods: The Connor-Davidson Resilience Scale (CDRS) score and serum ghrelin levels were assessed at baseline in 1,094 patients. The patients initially received antidepressant monotherapy. Patients with an insufficient response or uncomfortable side effects received alternative treatments every 3 weeks (at 3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. The individual and combined effects of the CDRS score (low vs. high) and serum ghrelin level (low vs. high) on 12-week remission were analyzed using logistic regression models after adjusting for relevant covariates.

Results: The individual effects of the CDRS score and serum ghrelin level on 12-week remission were not statistically significant. However, the high-CDRS, high-ghrelin group had a significantly higher 12-week remission rate compared to the low-CDRS, low-ghrelin group.

Conclusions: The combination of the CDRS score and serum ghrelin level is useful for predicting 12-week remission in patients with depressive disorders receiving pharmacotherapy.
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http://dx.doi.org/10.1016/j.jad.2021.09.039DOI Listing
September 2021

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data.

Int J Geriatr Psychiatry 2021 Sep 25. Epub 2021 Sep 25.

Division of Psychiatry, University College London, London, UK.

Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants.

Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008-16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis.

Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03-0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses.

Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.
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http://dx.doi.org/10.1002/gps.5625DOI Listing
September 2021

Relative risk of functional dyspepsia in patients with sleep disturbance: a population-based cohort study.

Sci Rep 2021 09 20;11(1):18605. Epub 2021 Sep 20.

Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan.

Increased prevalence of sleep disorders has been found in patients with functional dyspepsia; however, direction of causality remains unclear. Our aim was to compare the risk of incident functional dyspepsia between patients with and without sleep disturbance from a large population-based sample. Utilizing a nation-wide health insurance administrative dataset, we assembled an 11-year historic cohort study to compare subsequent incidence of diagnosed functional dyspepsia between adult patients with any diagnosis of sleep disturbance and age- and gender-matched controls. Hazard ratios adjusted for other relevant comorbidities and medications were calculated using Cox regression models. 45,310 patients with sleep disorder and 90,620 controls were compared. Patients with sleep apnea had a 3.3-fold (95% confidence interval: 2.82 ~ 3.89) increased hazard of functional dyspepsia compared with controls. This increased risk persisted regardless of previously diagnosed depression coexisted. Sleep disturbance was associated with an increased risk of subsequent functional dyspepsia. Potential mechanisms are discussed.
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http://dx.doi.org/10.1038/s41598-021-98169-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452703PMC
September 2021

Inequalities in glycemic management in people living with type 2 diabetes mellitus and severe mental illnesses: cohort study from the UK over 10 years.

BMJ Open Diabetes Res Care 2021 09;9(1)

Clinical Effectiveness Group, Institute of Population Health Sciences, Queen Mary, University of London, London, UK.

Introduction: Using data from a a primary care pay-for-performance scheme targeting quality indicators, the objective of this study was to assess if people living with type 2 diabetes mellitus (T2DM) and severe mental illnesses (SMI) experienced poorer glycemic management compared with people living with T2DM alone, and if observed differences varied by race/ethnicity, deprivation, gender, or exclusion from the scheme.

Research Design And Methods: Primary care data from a cohort of 56 770 people with T2DM, including 2272 people with T2DM and SMI, from London (UK), diagnosed between January 17, 2008 and January 16, 2018, were used. Adjusted mean glycated hemoglobin (HbA1c) and HbA1c differences were assessed using multilevel regression models.

Results: Compared with people with T2DM only, people with T2DM/SMI were more likely to be of an ethnic minority background, excluded from the pay-for-performance scheme and residing in more deprived areas. Across the sample, mean HbA1c was lower in those with T2DM and SMI (mean HbA1c: 58 mmol/mol; 95% CI 57 to 59), compared with people with T2DM only (mean HbA1c: 59 mmol/mol; 95% CI 59 to 60). However, HbA1c levels were greater in Bangladeshi, Indian, Pakistani, and Chinese people compared with the White British reference in the T2DM/SMI group. People with T2DM/SMI who had been excluded from the pay-for-performance scheme, had HbA1c levels which were +7 mmol/mol (95% CI 2 to 11) greater than those with T2DM/SMI not excluded. Irrespective of SMI status, increasing deprivation and male gender were associated with increased HbA1c levels.

Conclusions: Despite a pay-for-performance scheme to improve quality standards, inequalities in glycemic management in people with T2DM and SMI persist in those excluded from the scheme and by gender, ethnicity, and area-level deprivation.
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http://dx.doi.org/10.1136/bmjdrc-2021-002118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438718PMC
September 2021

Associations Between COVID-19 Symptoms and Psychological Distress.

Front Psychiatry 2021 17;12:721532. Epub 2021 Aug 17.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea.

Hospital isolation for COVID-19 may cause significant psychological stress. The association between COVID-19 symptoms and psychological symptoms has not been systematically studied. We investigated the effects of telephonic intervention on the relationship between psychological symptoms and COVID-19 symptoms at the time of hospitalization and 1 week later. We screened 461 patients with COVID-19 for psychiatric symptoms from February 29, 2020, to January 3, 2021. In total, 461 patients were evaluated 2 days after admission, and 322 (69.8%) were followed 1 week later. To assess anxiety and depressive symptoms, the Hospital Anxiety and Depression Scale (HADS) was administered to patients once per week. The Insomnia Severity Index (ISI) and item 9 of the Beck Depression Inventory (BDI-9) were used weekly to assess insomnia and suicidal ideation. Of 461 enrolled patients, we observed clinically meaningful psychological anxiety symptoms (in 75/16.3% of patients), depression (122/26.5%), insomnia (154/33.4%), and suicidal ideation (54/11.7%). Commonly reported COVID-19 symptoms are cough/sputum/sneezing (244, 52.9%), headache/dizziness (98, 21.3%), myalgia (113, 24.5%), and sore throat (89, 19.3%). Compared to baseline, significant improvements were found in anxiety, depression, and suicidal ideation at 1 week. No significant group differences in ISI score were observed. COVID-19 symptoms at baseline had a significant and persistent negative impact on anxiety and depression at admission and at 1 week after hospitalization. Early intervention is essential to improve the outcomes of patients with mental illness.
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http://dx.doi.org/10.3389/fpsyt.2021.721532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415963PMC
August 2021

Real-world experience of assessing antibodies against the N-methyl-D-aspartate receptor (NMDAR-IgG) in psychiatric patients. A retrospective single-centre study.

Brain Behav Immun 2021 Nov 1;98:330-336. Epub 2021 Sep 1.

King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; South London and Maudsley NHS Foundation Trust, London, UK.

Objective: To evaluate the frequency of anti-NMDAR encephalitis in a secondary mental health service and investigate the challenges of its diagnosis in routine clinical practice.

Methods: Patients whose electronic health records registered an indication for NMDAR-IgG assessment were selected and seropositive patients were reviewed.

Results: In 1661 patients assessed for NMDAR-IgG over 12 years, the positivity rate was 3.79% (95% confidence interval [CI]: 2.87-4.70%). The working diagnosis at assessment was new onset psychosis in 38.7% and a chronic psychotic syndrome in 34.0%. Among seropositive patients, 30 (47.6%, 95%CI: 35.8-59.7%) had a final alternative diagnosis different from encephalitis after a median period of 49 months from onset. Patients with a final diagnosis of encephalitis were more frequently female (27/35 vs 13/30, p = 0.011) than other seropositive patients and had more frequently an acute (34/35 vs 11/30, p < 0.001), fluctuating (21/23 vs 4/27, p < 0.001) or agitated (32/32 vs 10/26, p < 0.001) presentation. Nine encephalitic patients received specialized follow-up for chronic neuropsychiatric problems including learning disabilities, organic personality disorder, anxiety, fatigue, obsessive-compulsive and autism-like disorder.

Conclusions: In a psychiatric setting, NMDAR-IgG seropositivity rates were low with a positive predictive value for encephalitis around 50% when screened patients had chronic presentations and absence of other diagnostic criteria for encephalitis or psychosis of autoimmune origin. Chronic neuropsychiatric problems in anti-NMDAR encephalitis are not uncommon, so better diagnostic and treatment strategies are still needed.
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http://dx.doi.org/10.1016/j.bbi.2021.08.233DOI Listing
November 2021

Predictive values of tumor necrosis factor-α for depression treatment outcomes: effect modification by hazardous alcohol consumption.

Transl Psychiatry 2021 09 2;11(1):450. Epub 2021 Sep 2.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.

Inflammation is potentially associated with poor antidepressant treatment outcomes. Pro-inflammatory cytokines are influenced by hazardous alcohol consumption. The aim of the present study was to investigate the effects of the serum tumor necrosis factor-α (sTNF-α) level on antidepressant treatment outcomes in terms of the 12-week and 12-month remission rates and 24-month relapse rate, and to investigate the potential modifying effects of alcohol consumption on these associations in patients with depressive disorders. At baseline, sTNF-α was measured and alcohol-related data from the Alcohol Use Disorders Identification Test (AUDIT) and consumption history were collected from 1094 patients. Patients received stepwise antidepressant treatment. Remission at 12 weeks and 12 months was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7. Relapse (HAMD score ≥ 14) was identified until 24 months for those who had initially responded (HAMD score <14) at 12 weeks. Higher sTNF-α levels were found to have significant effects on the 12-week and 12-month non-remission and 24-month relapse rates. These effects were more prominent in those with low levels of alcohol consumption (AUDIT score ≤ 8 or no current alcohol consumption); the effects were not significant in those exhibiting hazardous alcohol consumption (AUDIT score > 8 or current drinking). Significant interactions were found for the 12-month non-remission and relapse rates, although the interaction was not statistically significant for 12-week remission. In conclusion, baseline sTNF-α levels may be a useful predictor for both short- and long-term antidepressant treatment outcomes, and the consideration of alcohol consumption status may increase predictability, in particular for long-term outcomes.
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http://dx.doi.org/10.1038/s41398-021-01581-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413287PMC
September 2021

Centrally Acting Anticholinergic Drugs Used for Urinary Conditions Associated with Worse Outcomes in Dementia.

J Am Med Dir Assoc 2021 Aug 30. Epub 2021 Aug 30.

King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.

Objectives: To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms.

Design: Retrospective cohort study.

Setting And Participants: Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database.

Methods: Central anticholinergic burden related to bladder drugs was estimated using the anticholinergic effect on cognition scale. Data were linked to national mortality and hospitalization data sources, and serially recorded Mini-Mental State Examination scores were used to investigate cognitive decline.

Results: Patients had a median survival of 4.1 years. Urinary drugs with a high anticholinergic effect on cognition score (tolterodine, oxybutynin) were associated with a 55% increased mortality risk (hazard ratio 1.55; 95% confidence interval 1.19‒2.01; P = .001) compared with drugs with low or no central anticholinergic burden (darifenacin, fesoterodine, trospium, mirabegron, solifenacin). Cognitive decline over a 24-month period around diagnosis was only detectable in the high central anticholinergic group, but there was no significant difference in cognitive trajectories between the high and low/no anticholinergic bladder drug groups. No increase of emergency hospitalization risk was seen in relation to central anticholinergic burden.

Conclusions And Implications: Urinary drugs with high central anticholinergic burden cause more harm than those acting peripherally and should be avoided in people with dementia. Further research is needed to test whether centrally acting anticholinergic agents in general cause worse outcomes in dementia.
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http://dx.doi.org/10.1016/j.jamda.2021.08.011DOI Listing
August 2021

Health status risk factors and quality of life in 75-84-year-old individuals assessed for dementia using the short 10/66 dementia diagnostic schedule.

PeerJ 2021 19;9:e12040. Epub 2021 Aug 19.

Institute of Psychiatry, Psychology and Neuroscience, King's College London,, London, United Kingdom.

Background: Trinidad is an island that not only has a population at high vascular risk but also one that is in epidemiological transition with high dementia prevalence. The aim of the study was to investigate modifiable risk factors associated with dementia in middle-old (75-84 years) individuals.

Methods: As part of a large national community survey of dementia prevalence in Trinidad, 811 people aged 75-84 years were evaluated for dementia using the 10/66 short algorithm. Demographic data collected included information on age, gender, ethnicity, religion, education, occupation, living accommodation, smoking, alcohol consumption, self-reported medical conditions, impairments and ability to do instrumental activities of daily living (IADL). Data were analysed using multivariable logistic regression models.

Results: Of the 811 participants, nearly 55% were female. The mean age was 78.8 (SD = 2.8) years and dementia was present in 198 (24.4%). Having less than ten years of education, being an agricultural worker, skilled labourer or housewife and having more than four co-morbidities were significantly associated with dementia. The odds ratio for dementia for those having self-reported stroke was 4.93 (95% CI [2.64-9.23]) and for diabetes was 1.76 (95% CI [1.17-2.65]) adjusting for age, age, gender, ethnicity, religion, education and occupation. Impairment in eyesight, hearing, climbing stairs, and walking were also more common in the group with dementia. Ability to perform IADLs was linked with dementia. Individuals with dementia were more likely to be unable to perform any of the eight IADLs. Those who did not exercise at all (OR 6.95, 95% CI [2.02-23.90]) and those who did low exercise (OR 1.83, 95% CI [1.07-3.13]) compared to those who did moderate to high exercise were also more likely to have dementia.

Conclusion: In the middle-old population in Trinidad having diabetes and stroke, low IADL score, and no exercise were more common in people with dementia.
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http://dx.doi.org/10.7717/peerj.12040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380427PMC
August 2021

What gets recorded, counts: dementia recording in primary care compared with a specialist database.

Age Ageing 2021 Aug 21. Epub 2021 Aug 21.

King's College London Institute of Psychiatry Psychology and Neuroscience, London, UK.

Background: databases of electronic health records are powerful tools for dementia research, but data can be influenced by incomplete recording. We examined whether people with dementia recorded in a specialist database (from a mental health and dementia care service) differ from those recorded in primary care.

Methods: a retrospective cohort study of the population covered by Lambeth DataNet (primary care electronic records) between 2007 and 2019. Documentation of dementia diagnosis in primary care coded data and linked records in a specialist database (Clinical Records Interactive Search) were compared.

Results: 3,859 people had dementia documented in primary care codes and 4,266 in the specialist database, with 2,886/5,239 (55%) documented in both sources. Overall, 55% were labelled as having Alzheimer's dementia and 29% were prescribed dementia medication, but these proportions were significantly higher in those documented in both sources. The cohort identified from the specialist database were less likely to live in a care home (prevalence ratio 0.73, 95% confidence interval 0.63-0.85), have multimorbidity (0.87, 0.77-0.98) or consult frequently (0.91, 0.88-0.95) than those identified through primary care codes, although mortality did not differ (0.98, 0.91-1.06).

Discussion: there is under-recording of dementia diagnoses in both primary care and specialist databases. This has implications for clinical care and for generalizability of research. Our results suggest that using a mental health database may under-represent those patients who have more frailty, reflecting differential referral to mental health services, and demonstrating how the patient pathways are an important consideration when undertaking database studies.
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http://dx.doi.org/10.1093/ageing/afab164DOI Listing
August 2021

Predictors and outcomes of experienced and anticipated discrimination in patients treated for depression: A 2-year longitudinal study.

J Affect Disord 2021 Nov 18;294:761-768. Epub 2021 Jul 18.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address:

Background: Stigma is both common and associated with greater depressive morbidity in depressives. Surprisingly few longitudinal studies have explored the predictors and consequences of stigma and discrimination.

Method: A total of 230 patients with depression who were commencing treatment were enrolled. Experienced and anticipated discrimination were assessed using the Discrimination and Stigma Scale at the 1-year follow-up. The Hamilton Rating Scale for Depression, Hospital Anxiety and Depression Scale, Clinical Global Impression Scale-Severity, Social and Occupational Functioning Assessment Scale (SOFAS), EuroQol-5 Dimension (EQ-5D) questionnaire, and Sheehan Disability Scale were administered at baseline, 1 year, and 2 years, to assess various depression outcomes. Baseline personality was evaluated using the Big Five Inventory-10.

Results: A previous depressive history and low agreeableness predicted experienced discrimination; a higher level of education, non-married status, and higher functional disability predicted anticipated discrimination. Higher-level experienced discrimination during the first year of treatment was significantly associated with poorer improvements in all six measured outcomes after 1 year of treatment, and again after 2 years of treatment (with the exception of the EQ-5D score). Higher anticipated discrimination was significantly associated with less improvement in the SOFAS scores after both 1 and 2 years of treatments.

Limitations: The study was a single-center work; this maximized consistency but may limit generalizability.

Conclusions: Discrimination exerts negative effects on depression outcomes that can be predicted at the initiation of treatment. Interventional studies are required to prevent and manage stigmatization of persons with depression.
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http://dx.doi.org/10.1016/j.jad.2021.07.049DOI Listing
November 2021

Risk of hospitalised falls and hip fractures in working age adults receiving mental health care.

Gen Hosp Psychiatry 2021 Sep-Oct;72:81-87. Epub 2021 Jul 20.

Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom.

Objective: This retrospective cohort study investigates risks of hospitalised fall or hip fractures in working age adults receiving mental health care in South London.

Methods: Patients aged 18 to 64, who received a first mental illness diagnosis between 2008 and 2016 were included. Primary outcome was hospitalised falls, secondary outcome was hip fractures. Age- and gender-standardised incidence rates and incidence rate ratios (IRRs) compared to local general population were calculated. Multivariate Cox proportionate hazard models were used to investigate which mental health diagnoses were most at risk.

Results: In 50,885 patients incidence rates were 8.3 and 0.8 per 1,000 person-years for falls and hip fractures respectively. Comparing mental health patients to the general population, age-and-gender-adjusted IRR for falls was 3.6 (95% CI: 3.3-4.0) and for hip fractures 7.5 (95% CI: 5.2-10.4). The falls IRR was highest for borderline personality and bipolar disorder and lowest for schizophreniform and anxiety disorder. After adjusting for multiple confounders in the sample of mental health service users, borderline personality disorder yielded a higher and anxiety disorder a lower falls risk.

Conclusion: Working age adults using mental health services have almost four times the incidence of hospitalised falls compared to general population. Targeted interventions are warranted.
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http://dx.doi.org/10.1016/j.genhosppsych.2021.07.006DOI Listing
July 2021

Quality indicators for dementia and older people nearing the end of life: A systematic review.

J Am Geriatr Soc 2021 Jul 31. Epub 2021 Jul 31.

Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care, Cicely Saunders Institute, King's College London, London, UK.

Background: Robust quality indicators (QIs) are essential for monitoring and improving the quality of care and learning from good practice. We aimed to identify and assess QIs for the care of older people and people with dementia who are nearing the end of life and recommend QIs for use with routinely collected electronic data across care settings.

Methods: A systematic review was conducted, including five databases and reference chaining. Studies describing the development of QIs for care of older people and those with dementia nearing the end of life were included. QIs were categorized as relating to processes or outcomes, and mapped against six care domains. The psychometric properties (acceptability, evidence base, definition, feasibility, reliability, and validity) of each QI were assessed; QIs were categorized as robust, moderate, or poor.

Results: From 12,980 titles and abstracts screened, 37 papers and 976 QIs were included. Process and outcome QIs accounted for 780 (79.7%) and 196 (20.3%) of all QIs, respectively. Many of the QIs concerned physical aspects of care (n = 492, 50.4%), and very few concerned spiritual and cultural aspects of care (n = 19, 1.9%). Three hundred and fifteen (32.3%) QIs were robust and of those 220 were measurable using routinely collected electronic data. The final shortlist of 71 QIs came from seven studies.

Conclusions: Of the numerous QIs developed for care of older adults and those with dementia nearing the end of life, most had poor or moderate psychometric properties or were not designed for use with routinely collected electronic datasets. Infrastructure for data availability, combined with use of robust QIs, is important for enhancing understanding of care provided to this population, identifying unmet needs, and improving service provision.
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http://dx.doi.org/10.1111/jgs.17387DOI Listing
July 2021

Interstitial Brachytherapy for Orbital Sebaceous Carcinoma.

Ophthalmic Plast Reconstr Surg 2021 Jul 27. Epub 2021 Jul 27.

The Department of Ocular Tumor, Orbital Disease and Ophthalmic Radiation Therapy, The New York Eye Cancer Center, New York, New York, U.S.A. The Departments of Radiation Oncology and Ophthalmology, The New York Eye and Ear Infirmary of Mount Sinai, New York, New York, U.S.A.

Sebaceous carcinoma is characterized by its aggressive local tumor behavior and ability to metastasize. Small periocular sebaceous carcinoma are typically treated by excision with cryotherapy. Larger tumors often require adjuvant external beam radiotherapy (EBRT) and/or exenteration surgery. When used alone, EBRT techniques typically exceed the tolerance of critical normal ocular structures. The interstitial orbital brachytherapy-boost technique permits dose escalation to the tumor bed, while minimizing radiation dose to critical normal ocular structures. Here, we present a case of orbital sebaceous carcinoma treated with excision, cryotherapy, and super-thick amniotic membrane fornix reconstruction. Then, after 3 weeks of healing, adjuvant-combined electron interstitial high-dose rate brachytherapy-boost was added to electron-beam radiotherapy to optimize the orbital radiation dose distribution, increase dose to inferonasal orbit, and allow relative sparing of orbital tissues. At 1-year follow-up, there was no evidence of orbital tumor, no significant eye lash loss, normal ocular motility, no radiation retinopathy, optic neuropathy and a visual acuity of 20/20.
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http://dx.doi.org/10.1097/IOP.0000000000002031DOI Listing
July 2021

Centrally-acting anticholinergic drugs- associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs.

Aging Ment Health 2021 Jul 26:1-9. Epub 2021 Jul 26.

Mental Health for Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, UK.

Objectives: Long-term use of anticholinergic medication in older people is associated with increased risk of cognitive decline and mortality, but this relationship could be confounded by the underlying illness the drugs are treating. To investigate associations between central anticholinergic antidepressants or antipsychotics and mortality, hospitalisation and cognitive decline in people with dementia.

Method: In cohorts of patients with a dementia diagnosis receiving antidepressant and/or antipsychotic medication ( = 4,380 and  = 2,335 respectively), assembled from a large healthcare database, central anticholinergic burden scores were estimated using the Anticholinergic Effect on Cognition (AEC) scale. Data were linked to national mortality and hospitalisation data sources, and Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline.

Results: There was a reduced mortality risk in people receiving agents with high central anticholinergic burden compared to those with no or low burden which was statistically significant in the antidepressant cohort (Hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.79-0.98;  = 0.023) but not the antipsychotic one (HR: 0.91; 95% CI: 0.82-1.02;  = 0.105). Patients on antidepressants with no central anticholinergic burden had accelerated cognitive decline compared with other groups, whereas no differences were found in the antipsychotic cohort. No significant associations were detected between antidepressant or antipsychotic-related central anticholinergic burden and hospitalisation.

Conclusion: These counter-intuitive findings may reflect factors underlying the choice of psychotropics rather than the agents themselves, although do not support a strong role for central anticholinergic drug actions on dementia outcomes. Further studies, including randomized switching of agents are needed to clarify this relationship.
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http://dx.doi.org/10.1080/13607863.2021.1947967DOI Listing
July 2021

Perinatal mental health around the world: priorities for research and service development in Africa.

BJPsych Int 2020 Aug;17(3):56-59

Senior Clinical Research Fellow, Division of Psychiatry, University of Edinburgh, Scotland. Email:

Africa is a diverse and changing continent with a rapidly growing population, and the mental health of mothers is a key health priority. Recent studies have shown that: perinatal common mental disorders (depression and anxiety) are at least as prevalent in Africa as in high-income and other low- and middle-income regions; key risk factors include intimate partner violence, food insecurity and physical illness; and poor maternal mental health is associated with impairment of infant health and development. Psychological interventions can be integrated into routine maternal and child healthcare in the African context, although the optimal model and intensity of intervention remain unclear and are likely to vary across settings. Future priorities include: extension of research to include neglected psychiatric conditions; large-scale mixed-method studies of the causes and consequences of perinatal common mental disorders; scaling up of locally appropriate evidence-based interventions, including prevention; and advocacy for the right of all women in Africa to safe holistic maternity care.
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http://dx.doi.org/10.1192/bji.2020.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281281PMC
August 2020

Developing Biopsychosocial Research on Maternal Mental Health in Malawi: Community Perspectives and Concerns.

Ethics Hum Res 2021 Jul;43(4):11-19

Professor at the Usher Institute at the Edinburgh Medical School.

Interest in maternal mental health research is growing around the world. Maternal mental health research studies in Malawi have, for instance, sought to determine and establish the incidence and prevalence of depression and anxiety in pregnant people and the factors that contribute to experiences of these states. This article reports stakeholder perspectives on potential community concerns with biopsychosocial mental health research (which might include collecting blood samples) in Malawi. These perspectives were generated through a town hall event that featured five focus group discussions with various participants. In this article, we reflect on key themes from these discussions, demonstrating the endurance of long-standing concerns and practices around autonomy, consent, and the drawing of blood. We conclude by arguing that, while maternal mental health research conducted in Malawi could benefit Malawian women and children, consultation with community stakeholders is necessary to inform whether and how such research should be conducted.
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http://dx.doi.org/10.1002/eahr.500095DOI Listing
July 2021

Predictors of relapse following a stepwise psychopharmacotherapy regime in patients with depressive disorders.

J Affect Disord 2021 10 18;293:109-116. Epub 2021 Jun 18.

Department of Psychiatry, Chonnam National University Medical School, 160 Baekseoro, 12 Dong-gu, Gwangju 61469, Republic of Korea.

Background: Real world predictors of relapse following routine treatment for depression remain under-researched. We sought to investigate this in an outpatient clinical sample with depressive disorders receiving stepwise pharmacotherapy based on early clinical decision-making, applying a naturalistic 24-month prospective design.

Methods: Patients were recruited at a University hospital in South Korea from March 2012 to April 2017. After 3-week antidepressant monotherapy (N = 1262), next treatment steps (1, 2, 3, and 4 or over) with alternative strategies (switching, augmentation, combination, and mixtures of these approaches) were administered based on measurements and patient preference at 3-week points in the acute treatment phase (3, 6, 9, and 12 weeks) (N = 1246). For those who responded [Hamilton Depression Rating Scale (HAMD) score of≤14] (N = 937), relapse (HAMD>14) was identified every 3 months from 6 to 24 months (N = 816). Predictors of relapse were evaluated using multi-variate Cox proportional hazards models.

Results: Four independent relapse predictors were identified: higher number of previous depressive episodes, higher anxiety at baseline, higher number of treatment steps, and poor medication adherence. In particular, treatment Step 4 was significantly associated with relapse compared to treatment Step 1, 2, and 3 after adjustment for relevant covariates.

Limitation: Withdrawal syndromes after discontinuing psychotropic drugs, known to confound the determination of relapse, were not evaluated. The study was conducted at a single site, which maximised consistency but may limit generalizability.

Conclusions: Predictors of relapse reported from more restricted trial or cohort samples were replicated in this long-term naturalistic prospective design.
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http://dx.doi.org/10.1016/j.jad.2021.06.015DOI Listing
October 2021

Multi-domain clinical natural language processing with MedCAT: The Medical Concept Annotation Toolkit.

Artif Intell Med 2021 07 1;117:102083. Epub 2021 May 1.

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Health Data Research UK London, University College London, London, UK; Institute of Health Informatics, University College London, London, UK; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. Electronic address:

Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of information extraction (IE) technologies to enable clinical analysis. We present the open source Medical Concept Annotation Toolkit (MedCAT) that provides: (a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; (b) a feature-rich annotation interface for customizing and training IE models; and (c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ∼8.8B words from ∼17M clinical records and further fine-tuning with ∼6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases.
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http://dx.doi.org/10.1016/j.artmed.2021.102083DOI Listing
July 2021

Fluorescent toxins as ion channel activity sensors.

Methods Enzymol 2021 12;653:295-318. Epub 2021 Apr 12.

Department of Physiology & Membrane Biology, University of California, Davis, CA, United States; Department of Anesthesiology & Pain Medicine, University of California, Davis, CA, United States. Electronic address:

Voltage gated ion channels (VGICs) shape the electrical character of cells by undergoing structural changes in response to membrane depolarization. High-resolution techniques have provided a wealth of data on individual VGIC structures, but the conformational changes of endogenous channels in live cell membranes have remained unexplored. Here, we describe methods for imaging structural changes of voltage-gated K channels in living cells, using peptidyl toxins labeled with fluorophores that report specific protein conformations. These Endogenous Voltage-sensor Activity Probes (EVAPs) enable study of both VGIC allostery and function in the context of endogenous live-cell membranes under different physiological states. In this chapter, we describe methods for the synthesis, imaging, and analysis of dynamic EVAPs, which can report K channel activity in complex tissue preparations via 2-photon excitation microscopy, and environment-sensitive EVAPs, which report voltage-dependent conformational changes at the VGIC-toxin interface. The methods here present the utility of current EVAPs and lay the groundwork for the development of other probes that act by similar mechanisms. EVAPs can be correlated with electrophysiology, offering insight into the molecular details of endogenous channel function and allostery in live cells. This enables investigation of conformational changes of channels in their native, functional states, putting structures and models into a context of live-cell membranes. The expansive array of state-dependent ligands and optical probes should enable probes more generally for investigating the molecular motions of endogenous proteins.
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http://dx.doi.org/10.1016/bs.mie.2021.02.014DOI Listing
June 2021

Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.

Transl Psychiatry 2021 06 3;11(1):343. Epub 2021 Jun 3.

The Affiliated Hospital of Qingdao University & The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, 266003, PR China.

Background: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN).

Methods: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC).

Results: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis.

Conclusions: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.
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http://dx.doi.org/10.1038/s41398-021-01470-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175348PMC
June 2021

Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer.

Cancers (Basel) 2021 May 24;13(11). Epub 2021 May 24.

Department of Psychological Medicine, King's College London, London SE5 8AF, UK.

Background: We aimed to investigate the associations of breast cancer (BC) and cancer-related chemotherapies with cytokine levels, and cognitive function.

Methods: We evaluated subjective and objective cognitive function in BC patients before chemotherapy and 3~9 months after the completion of chemotherapy. Healthy volunteers without cancer were also compared as control group. Interleukins (IL) 2, 4, 5, 6, 10, 12p70, 13, 17A, 1β, IFNγ, and TNFα were measured. Associations of cancer status, chemotherapy and cytokine levels with subjective and objective cognitive impairments were analyzed using a regression model, adjusting for covariates, including IQ and psychological distress.

Results: After adjustment, poorer performance in semantic verbal fluency was found in the post-chemotherapy subgroup compared to controls ( = 0.011, = 0.070); whereas pre-chemotherapy patients scored higher in subjective cognitive perception. Higher IL-13 was associated with lower semantic verbal fluency in the post-chemotherapy subgroup. Higher IL-10 was associated with better perceived cognitive abilities in the pre-chemotherapy and control groups; while IL-5 and IL-13 were associated with lower perceived cognitive abilities in pre-chemotherapy and control groups. Our findings from mediation analysis further suggest that verbal fluency might be affected by cancer status, although mediated by anxiety.

Conclusions: Our findings suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Different cytokines and their interactions may have different roles of neuroinflammation or neuroprotection that need further research.
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http://dx.doi.org/10.3390/cancers13112576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197334PMC
May 2021

Vascular surgery receipt and outcomes for people with serious mental illnesses: Retrospective cohort study using a large mental healthcare database in South London.

J Psychosom Res 2021 Aug 20;147:110511. Epub 2021 May 20.

King's College London (Institute of Psychiatry, Psychology and Neuroscience), London, United Kingdom. Electronic address:

Objective: Vascular surgery can be common among people with serious mental illness (SMI) given the high prevalence of cardiovascular disease. However, post-operative outcomes following vascular surgery have received little investigation, particularly in a subpopulation of SMI.

Methods: We conducted a retrospective observational study using data from the South London and Maudsley NHS Foundation Trust (SLaM) via its Clinical Record Interactive Search (CRIS) platform and linkage with Hospital Episode Statistic (HES). Vascular surgery recipients were identified using OPCS version 4 codes. Length of stay (LOS) was modelled using Incidence Rate Ratios (IRRs), and 30-day emergency hospital readmissions using Odds Ratios (ORs) for people with SMI compared with the general population.

Results: Vascular surgery was received by 152 patients with SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) and 8821 catchment residents without any mental health conditions. People with active SMI symptoms more likely to be admitted to hospital via emergency route OR: 1.80 (95% CI: 1.06, 3.07) and more likely to stay longer in the hospital for vascular surgery IRR: 1.35 (1.01, 1.80) and more likely to be readmitted to hospital via emergency route within 30 days OR: 1.53 (1.02, 2.67). People with SMI who had major open vascular surgery and peripheral endovascular surgery more likely to have worse post-operative outcomes.

Conclusion: Our study highlights the risks faced by people with SMI following vascular surgery. These suggest tailored guidelines and policies are needed, based on the identification of pre-operative risk factors, allowing for focused post-vascular surgery care to minimise adverse outcomes.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110511DOI Listing
August 2021

Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.

BMJ Open 2021 05 26;11(5):e049721. Epub 2021 May 26.

Department of Biostatistics and Health Informatics, King's College London Institute of Psychiatry, Psychology and Neuroscience, London, UK.

Objectives: To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.

Design: A regression discontinuity in time (RDiT) analysis of daily service-level activity.

Setting And Participants: Mental healthcare data were extracted from 10 UK providers.

Outcome Measures: Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.

Results: Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.

Conclusions: MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.
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http://dx.doi.org/10.1136/bmjopen-2021-049721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159668PMC
May 2021

Tumor control probability in hypofractionated radiotherapy as a function of total and hypoxic tumor volumes.

Phys Med Biol 2021 Jun 11;66(12). Epub 2021 Jun 11.

Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98004, United States of America.

Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the tumor control probability (TCP) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules. Compared to radiotherapy with conventional fractionation schedules, simulations of hypofractionated radiotherapy may require different models for cell survival and the oxygen enhancement ratio (OER). Our TCP simulations in hypofractionated radiotherapy are based on the LQ model and the universal survival curve (USC) developed for the high doses used in SBRT. The predicted trends in local control as a function of the initial tumor volume were evaluated in SBRT for non-small cell lung cancer (NSCLC). Our results show that both LQ and USC based models cannot describe the TCP reduction for larger tumor volumes observed in the clinical studies if the tumor is considered completely oxygenated. The TCP calculations are in agreement with the clinical data if the subpopulation of radio-resistant hypoxic cells is considered with the volume that increases as initial tumor volume increases. There are two conclusions which follow from our simulations. First, the extent of hypoxia is likely a primary reason of the TCP reduction with increasing the initial tumor volume in SBRT for NSCLC. Second, the LQ model can be an acceptable approximation for the TCP calculations in hypofractionated radiotherapy if the tumor response is defined primarily by the hypoxic fraction. The larger value of OER in the hypofractionated radiotherapy compared to the conventional radiotherapy effectively extends the applicability of the LQ model to larger doses.
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http://dx.doi.org/10.1088/1361-6560/ac047eDOI Listing
June 2021

Tumor control probability in hypofractionated radiotherapy as a function of total and hypoxic tumor volumes.

Phys Med Biol 2021 Jun 11;66(12). Epub 2021 Jun 11.

Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98004, United States of America.

Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the tumor control probability (TCP) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules. Compared to radiotherapy with conventional fractionation schedules, simulations of hypofractionated radiotherapy may require different models for cell survival and the oxygen enhancement ratio (OER). Our TCP simulations in hypofractionated radiotherapy are based on the LQ model and the universal survival curve (USC) developed for the high doses used in SBRT. The predicted trends in local control as a function of the initial tumor volume were evaluated in SBRT for non-small cell lung cancer (NSCLC). Our results show that both LQ and USC based models cannot describe the TCP reduction for larger tumor volumes observed in the clinical studies if the tumor is considered completely oxygenated. The TCP calculations are in agreement with the clinical data if the subpopulation of radio-resistant hypoxic cells is considered with the volume that increases as initial tumor volume increases. There are two conclusions which follow from our simulations. First, the extent of hypoxia is likely a primary reason of the TCP reduction with increasing the initial tumor volume in SBRT for NSCLC. Second, the LQ model can be an acceptable approximation for the TCP calculations in hypofractionated radiotherapy if the tumor response is defined primarily by the hypoxic fraction. The larger value of OER in the hypofractionated radiotherapy compared to the conventional radiotherapy effectively extends the applicability of the LQ model to larger doses.
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http://dx.doi.org/10.1088/1361-6560/ac047eDOI Listing
June 2021

Guidance for researchers wanting to link NHS data using non-consent approaches: a thematic analysis of feedback from the Health Research Authority Confidentiality Advisory Group.

Int J Popul Data Sci 2020 Oct 2;5(1):1355. Epub 2020 Oct 2.

Department of Psychological Medicine, King's College London, Strand, London WC2R 2LS, UK.

Introduction: The use of linked data and non-consent methodologies is a rapidly growing area of health research due to the increasing detail, availability and scope of routinely collected electronic health records data. However, gaining the necessary legal and governance approvals to undertake data linkage is a complex process in England.

Objectives: We reflect on our own experience of establishing lawful basis for data linkage through Section 251 approval, with the intention to build a knowledgebase of practical advice for future applicants.

Methods: Thematic analysis was conducted on a corpus of Section 251 feedback reports from the NHS Health Research Authority Confidentiality Advisory Group.

Results: Four themes emerged from the feedback. These were: (a) Patient and Public Involvement, (b) Establishing Rationale, (c) Data maintenance and contingency, and the need to gain (d) Further Permissions from external authorities prior to full approval.

Conclusions: Securing Section 251 approval poses ethical, practical and governance challenges. However, through a comprehensive, planned approach Section 251 approval is possible, enabling researchers to unlock the potential of linked data for the purposes of health research.
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http://dx.doi.org/10.23889/ijpds.v5i1.1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110887PMC
October 2020
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